Arendshorst W J, Brännström K, Ruan X
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, 27599-7545, USA.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S149-61.
Angiotensin II (AngII) exerts powerful effects on the renal microcirculation to influence a variety of functions. This review summarizes some of the major findings over the past 10 years as they elucidate the multiple roles that AngII plays in the regulation of whole kidney blood flow, perfusion of cortical and medullary regions, and renal autoregulation. Topics of discussion include localization of AngII receptor types and subtypes in the renal vasculature, action of AngII on vascular smooth muscle cells of the afferent and efferent arterioles, and intracellular signaling pathways. Within the microvasculature, AngII causes potent constriction in both the afferent and efferent arterioles, with responses modulated by paracrine and autocrine factors of endothelial and macula densa origins. With regard to renal autoregulatory mechanisms consisting of the myogenic response and the tubuloglomerular feedback mechanism, the myogenic response appears to operate independent of the renin-angiotensin system. On the other hand, tubuloglomerular feedback activity is often directly proportional to concentrations of AngII, especially in high renin states. Of the two types defined to date, the AT1 is the predominant receptor in the adult rat kidney mediating the vascular effects of AngII. AT2 receptor is highly expressed in the fetal kidney and is important for renal development, but is very weakly expressed in adult animals. Nevertheless, AT2 receptors may mediate vasodilation under certain conditions. The signaling transduction pathways for AT1 receptors include Gq/11-protein and protein kinase C activation. AngII causes constriction of the afferent arteriole primarily by stimulation of calcium entry via voltage-sensitive, L-type channels, whereas AngII effects on the efferent arteriole are due to calcium release from intracellular stores and calcium entry through voltage-independent calcium entry channels. Future experiments should contribute to a more in-depth understanding of the modulation of AngII effects by other vasoactive agents and interactions between different second-messenger signaling pathways in health and disease.
血管紧张素II（AngII）对肾微循环产生强大作用，从而影响多种功能。本综述总结了过去10年的一些主要研究发现，这些发现阐明了AngII在调节全肾血流量、皮质和髓质区域灌注以及肾自身调节中所起的多种作用。讨论的主题包括AngII受体类型和亚型在肾血管系统中的定位、AngII对入球小动脉和出球小动脉血管平滑肌细胞的作用以及细胞内信号通路。在微血管系统中，AngII会使入球小动脉和出球小动脉均发生强烈收缩，其反应受到内皮和致密斑来源的旁分泌和自分泌因子的调节。关于由肌源性反应和管球反馈机制组成的肾自身调节机制，肌源性反应似乎独立于肾素-血管紧张素系统发挥作用。另一方面，管球反馈活动通常与AngII浓度直接成正比，尤其是在高肾素状态下。在迄今确定的两种类型中，AT1是成年大鼠肾脏中介导AngII血管效应的主要受体。AT2受体在胎儿肾脏中高度表达，对肾脏发育很重要，但在成年动物中表达非常微弱。然而，AT2受体在某些情况下可能介导血管舒张。AT1受体的信号转导途径包括Gq/11蛋白和蛋白激酶C的激活。AngII主要通过刺激钙经电压敏感的L型通道进入细胞而导致入球小动脉收缩，而AngII对出球小动脉的作用则是由于细胞内钙库释放钙以及通过非电压依赖性钙内流通道进入钙。未来的实验应有助于更深入地了解其他血管活性药物对AngII效应的调节以及健康和疾病状态下不同第二信使信号通路之间的相互作用。
